IL6R and infection: Although IL-6 is often considered a pro-inflammatory cytokine, mechanistic studies have revealed a dichotomy between pro- and anti-inflammatory effects, which are facilitated by two distinct IL-6 signaling pathways (Figure 2) [51]: (1) the classic ligand-receptor pathway via membrane-bound IL-6R is responsible for anti-inflammatory and protective activities (e.g., infection defense) and (2) the trans-signaling pathway via circulating soluble IL-6R (sIL-6R), which triggers pro-inflammatory processes.